Methyl mercury (MeHg) has been shown to pose a severe health hazard and environmental contamination with mercury represents an important public health problem. Although there have been a number of studies on the effects of MeHg on the cell, to date relatively little is known about its effects on cellular nucleic acid synthesis at the molecular level. Previous workers have shown that methyl mercury inhibits the synthesis of DNA and RNA in cells in culture. We have shown that it also inhibits DNA synthesis, and for some cells, RNA synthesis, in vitro in isolated nuclei. We will investigate further the effects of MeHg on nucleic acid synthesis by studying its effects on the template activity of DNA in a DNA polymerase reaction, as well as in a DNA replication reaction in vitro. We will investigate whether initiation or elongation is specifically affected by MeHg. We will attempt to detect specific lesions caused by MeHg in double-stranded DNA. We will study the interaction of MeHg with chromatin by physical methods, as well as by examining its effect on the replication of chromatin in vitro. We will investigate whether MeHg has any effect on the process of cell transformation by chemicals or by tumor viruses. We will also investigate the basis for the different effects of MeHg on RNA synthesis in vitro in different cell types.